Funds are requested for a state-of-the-art triple quadrupole mass spectrometer (QqQ) and two essential ancillary attachments - an ultra-high pressure liquid chromatography (UPLC) system, and a High- Field Assymetric Waveform Ion Mobility Spectrometry (FAIMS) attachment. This equipment will be located in the Pasarow Mass Spectrometry Laboratory (PMSL) within the Semel (formerly Neuropsychiatric) Institute at UCLA, a campus-wide core mass spectrometry laboratory. The QqQ mass spectrometers currently in the PMSL are about 17 years old and these are obsolete by any criteria. In the intervening period there have been significant improvements in sensitivity, resolution, accuracy of m/z assignment, computer control, experimental flexibility, and detection dynamic range of these instruments. UPLC brings liquid chromatographic resolution close to that attainable with capillary gas chromatography, and is an important development for high sensitivity work, high throughput work, and for work with complex mixtures. There is no UPLC system on the UCLA campus. The FAIMS technology is a new development that for some compounds lowers the background from isobaric ions, and as such can provide a significant advantage for low molecular weight analyses of complex mixtures by LC/MS, as is intended for the new instrument. The research projects for which the equipment will be used involve quantitative and qualitative analyses of a diverse range of molecules, many but not all with relatively low molecular weights (generally less that 1500 Da), in a variety of milieu. Collectively these compounds are implicated in diverse phenomena including signal transduction, cellular communication, hormonal homeostasis, addictive processes, ageing, logical thought processing, immune responses and inflammation. The application includes descriptions of eighteen collaborating laboratories with mass spectrometric analysis essential to their research projects. These groups are expected to occupy approximately 90% of instrument time. The remaining instrument time will be used by other collaborating groups as needed. Funding support is in place for all the collaborating laboratories. The PMSL has the necessary infrastructure to maintain and support the new equipment. Professor Faull, the PI on this application and the Director of the PMSL, and Postdoctoral Research Fellow Christopher Ryan, PhD, will be responsible for the day-to-day operation and maintenance of the new equipment. The PI has a strong track- record for the effective use of equipment purchased through the NIH SIG mechanism. This application represents a critical component of an effort by the UCLA Semel Institute and School of Medicine to re-place obsolete equipment within the campus core laboratories with state-of-the-art instruments for cutting edge research in metabolomics and related fields. PUBLIC HEALTH RELEVANCE: The research for which the new equipment will be used is directly relevant to many aspects of human health and disease, including cancer, metabolic diseases, brain injury, viral infectivity, psychiatric diseases, and age-related neurological diseases including Alzheimer's and Parkinson's diseases. The frequency with which many of these diseases occur in Western society is rising as the population ages. Research equipment such as that requested is crucial for understanding the molecular basis of these diseases and continued progress on these important problems that significantly impact human health and well-being.